Professor Lu Wei interpreted the results of checkMate-870 research, Navuliu mono-anti-adding Chinese group of four major therapeutic characteristics!

hot wire! It is safe and reliable to infuse mAb with 240 mg fixed dose and 30 minutes infusion. It also has anti-tumor activity in patients with EGFR mutation / HBV infection! Introduction to Lu Shun Professor, chief physician, doctoral supervisor, second-class Professor, Shanghai leading talent, Shanghai outstanding academic leader, chief expert of national key special projects, enjoying special allowance of the State Council, director of Chest Hospital Affiliated to Shanghai Jiaotong University, director of Shanghai lung cancer clinical medical center, director of China Anti Cancer Association, chairman of lung cancer professional committee, standing committee of China Society of Clinical Oncology (CSCO) He is a member of the Cancer Society of the Chinese Medical Association, chairman of the Cancer Society of the Chinese Medical Association, vice president of the oncology branch of the Shanghai Medical Association, head of the specialist training program, deputy editor in chief of the Journal of thoracic oncology, an official journal of the international lung cancer research Association Editorial board member of oncologist, executive director of Shanghai anti cancer association, vice chairman of precision medicine branch of China Medical Biotechnology Association, as the person in charge, presided over one international cooperation project of the Ministry of science and technology; one national new drug innovation major project, two sub topics of 863 major projects; one general project of NSFC. Recently, the annual meeting of American Association for cancer research (AACR) announced the navulieu list The results of the phase IIIB phase IIIB study of anti-cancer in Asian (mainly Chinese) patients with advanced non-small cell lung cancer (NSCLC) have brought new evidence of evidence-based medicine for immunotherapy of NSCLC patients in China.in this regard, the "medical community" has the honor to invite Professor Lu Shun, the main researcher of checkmate-870 and affiliated Chest Hospital of Shanghai Jiaotong University, to interpret the experimental design and research results.four conclusions have been drawn in this study for the treatment of NSCLC patients in China: the first large sample confirmed the safety and reliability of navulizumab in the real world treatment in China, which is consistent with the previous key clinical research results at home and abroad; the safety of 240 mg fixed dose and 30 Min infusion of navulizumab in Chinese population is good, and the first way is 3 mg / kg, 60 min infusion Conclusion: the safety and anti-tumor activity of mAb navuliyab in the treatment of hepatitis B virus (HBV) infected population is good, and the anti-tumor activity of mAb is the same for the treatment of patients with high incidence of EGFR mutation in China.to adjust the drug use mode and challenge the real treatment status of lung cancer in China. Checkmate-870 is an open label phase IIIB clinical study, which includes patients with advanced NSCLC (including squamous cell carcinoma and non squamous cell carcinoma) who have previously received 1-2 line systemic therapy. They received 240 mg of PD-1 inhibitor nivolumab and 30 minutes intravenous infusion (once every 2 weeks) as second-line / third line treatment 。The aim of this study was to evaluate the efficacy and safety of navulizumab in the real world of China. A total of 400 Asian patients were enrolled, of whom 394 were Chinese.combined with the characteristics of lung cancer patients in China, 17 patients with HBV infection (HBV DNA < 500 IU / ml), some EGFR mutations (34 cases) and alk fusion (10 cases) were included in the study. These EGFR / ALK positive patients had received two systematic treatments including targeted therapy and chemotherapy.the primary end point of checkmate-870 was the incidence of high-level (grade 3-5) treatment-related selective adverse reactions (AES) in non HBV infected patients.the secondary end points included: the incidence of grade 3-5 treatment-related selective AES in patients with HBV infection, the safety of all patients, and the effectiveness of efficacy indicators including overall survival (OS), objective response rate (ORR), and progression free survival (PFS) in different subgroups (histological type, PD-L1 expression, HBV infection, EGFR mutation).for the study design, Professor Lu Shun mentioned that there were some restrictions on the inclusion conditions of the checkmate-078 study, such as excluding hepatitis B infection and EGFR / ALK positive patients.the research design of checkmate-870 takes the following three considerations into consideration: 1) China is actually a country with a high incidence of hepatitis B. about 10% - 14% of lung cancer patients in China have ever been infected with hepatitis B virus.based on this, the checkmate-870 study explored whether immunotherapy is safe for these patients.② EGFR mutations are high in Chinese lung cancer patients, and these patients were excluded from the checkmate-078 study. Therefore, these populations were included in the checkmate-870 study to evaluate the efficacy of navulizumab.③ with the deepening understanding of navulizumab, clinicians realized that 30 minutes fixed dose infusion may be safe and effective, and the United States has also approved the fixed dose administration method, so this administration method was designed in checkmate-870 to evaluate its efficacy and safety.Figure 1. The design of checkmate-870 study was that 240 mg (30 minutes) was safe and reliable, and had anti-tumor activity for EGFR / HBV patients ▍ 240 mg fixed dose was also suitable for Chinese patients. The results of checkmate-870 study showed that the 6-month OS rate of the total population was 75% (95% when the median follow-up time was 9.6 months CI: 70-79%), Orr was 15.5%, and median PFS was 3.7 months.in all patients, the incidence of grade 3-4 treatment-related AES was 12.8%, and the withdrawal rate of grade 3-4 treatment-related AES was 2.0%.this study suggested that the safety and efficacy of the 240 mg / kg (30 minute infusion) of navulizumab was similar to that of 3 mg / kg (60 min infusion) in the previous checkmate-078 study.Table 1. Summary of safety information of the checkmate-870 study. 2. The overall population OS curve of the checkmate-870 study. In this regard, Professor Lu Shun said: "the original administration method of navulizumab was 3mg / kg, and then it was approved for fixed dose administration in the United States. if the drug is administered according to the weight, the requirements for drug packaging and the drug delivery process are relatively complex. in addition, in a comparative study in the United States, it was found that there was not too much change in the fixed dose and the actual dose based on body weight of navulizumab, which was also an important part of the checkmate-870 study. in fact, Chinese patients may be smaller than those in the United States, with a median weight of about 60 kg (about 80 kg for American patients), and the standard dosage of 3 mg / kg body weight should be 180 mg (240 mg for American patients). therefore, we need to study whether 240mg is safe and effective in Chinese population, and the results of checkmate-870 show that although the drug dose is slightly increased compared with the checkmate-078 study, no new safety issues have been observed and the efficacy is comparable. "▍ navulizumab is safe and reliable in the treatment of HBV infected people. Among non HBV infected patients, the most common level 3-4 treatment-related selective AEs were liver (2.3%), skin (1.6%), lung (1.0%) and endocrine (0.8%). There was no grade 5 AES. in patients with HBV infection, the incidence of grade 3-5 treatment-related selective AES was 0%. in terms of efficacy, the orr of HBV infected patients was similar to that of non HBV infected patients (17.6% and 15.4%, respectively). the results suggest that navulizumab can be safely and effectively used in the treatment of this special population in China. Table 2. Summary of treatment-related selective adverse reactions in the checkmate-870 study, Professor Lu Shun said: "we are very concerned about the safety of navulizumab in patients with hepatitis B infection, so patients with stable HBV DNA < 500 UI / ml virus control were included in the study. results: under the control of antiviral drugs, the efficacy and safety of using navulizumab were not significantly affected. "▍ the efficacy was also demonstrated in EGFR patients treated with navulizumab. In the subgroup analysis of EGFR mutations, the orr of patients treated with navulizumab was 14.7%, which was similar to that of patients without EGFR mutation (ORR was 14.2%). the results of this study suggest that patients with EGFR mutations may be treated with navulizumab as a treatment option after previous targeted and chemotherapy failure. for the EGFR mutation subgroup results, Professor Lu Shun pointed out that from the overall survival rate and Orr and other curative effect data results, the effect of navulizumab in the treatment of EGFR mutation positive and negative patients was equivalent. Fig. 3. OS curve of EGFR mutation subgroup 3 The results of the study and subgroup analysis were consistent with the experimental results. The application of navulizumab in the real world of China has solid evidence. The international research checkmate-017 / 057 and the Chinese study checkmate-078 have already confirmed that navulizumab has an unshakable position in the second-line treatment of NSCLC. However, in the actual clinical use, it is affected by the characteristics of the patient's disease and the association with the disease With the influence of complex factors such as disease, age and basic physical condition, the efficacy and safety of drugs may be different from the clinical research results, so the research results in the real world of drugs are of great significance. the results of the checkmate-870 study for the first time confirmed the efficacy and safety of navulizumab in real-world second-line and third-line treatment. checkmate-870 gives a satisfactory response to the real world immunotherapy for lung cancer in China. According to the results of the checkmate-870 study, Professor Lu Shun concluded that this study is a real-world study, so it can better reflect the real-world characteristics of patients, such as EGFR mutation, hepatitis B infection, and the efficacy and safety of using navulizumab in older people. this study, as the largest sample of second-line treatment of navulizumab in China, once again proves that the safety and efficacy of second-line use of navulizumab in real-world population is certain. Br / > the efficacy and safety of several large-scale second-line therapies have been confirmed in China. we hope that immunotherapy will go forward bravely, get more treatment evidence and benefit more cancer patients. reference: Shun Lu, Ying Cheng, Jianying Zhou, et al. Flat dose nivolumab (nivo) as second line (2L) treatment (TX) for Asian patients (PTS) with advanced non small cell lung cancer (NSCLC): checkmate 870. 2020 AACR